Acetic Acid → HCID 67497262, compound

HRID 1628236Notes

Reaction equation

HRID 1628236 reaction equation
[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:3]([NH:5][C:6]1[C:7]([O:17][CH3:18])=[N:8][CH:9]=[C:10]([C:12]2[CH:13]=[N:14][NH:15][CH:16]=2)[CH:11]=1)=[O:4].N[C@@H:27]([CH2:43]C1C=CC=CC=1)[C:28]([NH:30][C:31]1C(=O)NC=C(C2C=NNC=2)C=1)=O.[S:50]1C=C(C=O)N=C1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl>[CH3:18][O:17][C:7]1[C:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][CH2:43][C:27]2[S:50][CH:31]=[N:30][CH:28]=2)[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:11][C:10]([C:12]2[CH:13]=[N:14][NH:15][CH:16]=2)=[CH:9][N:8]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67497155HCID 67497155, compoundHCID 67497737HCID 67497737, compound

Product 1

HCID 67497262HCID 67497262, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of a 1:9 mixture of (2S)-2-amino-N-(2-methoxy-5-(1H-pyrazol-4-yl)pyridin-3-yl)-3-phenylpropanamide 15.1.D and (S)-2-amino-N-(2-oxo-5-(1H-pyrazol-4-yl)-1,2-dihydropyridin-3-yl)-3-phenylpropanamide (90 mg, 0.28 mmol) in DCM (1 mL) was added thiazole-4-carbaldehyde (26 mg, 0.28 mmol) and was then stirred for 1 hour. Sodium triacetoxyborohydride (170 mg, 0.82 mmol) and acetic acid (16 μL, 0.28 mmol) was then added, the mixture was stirred for an additional 1 hour at room temperature, concentrated and the crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA) to afford (2S)—N-(2-methoxy-5-(1H-pyrazol-4-yl)pyridin-3-yl)-3-phenyl-2-(thiazol-5-ylmethylamino)propanamide 15.1 (5.7 mg, 57%) as a white solid. LCMS ESI (pos.) m/e: 435.1 (M+1): 1H NMR (500 MHz, MeOH-D4) δ ppm 9.13 (d, J=1.83 Hz, 1H), 8.50 (d, J=1.83 Hz, 1H), 8.15 (d, J=1.83 Hz, 1H), 7.94 (s, 2H), 7.80 (d, J=1.83 Hz, 1H), 7.25-7.39 (m, 5H), 4.46-4.56 (m, 3H), 3.91 (s, 3H), 3.41 (dd, J=13.43, 6.10 Hz, 1H), 3.24 (dd, J=13.43, 9.16 Hz, 1H).

Workup

  1. stirringthe mixture was stirred for an additional 1 hour at room temperature
  2. concentrationconcentrated
  3. customthe crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA)

Sources & evidence

ORD record
ord-1b05aee01e384b7e920bd73131d1244a
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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